Vinylogous Mannich Cyclization for the Stereoselective Construction of trans ‐2‐Alkenyl‐3‐Aminophenyl‐Dihydrobenzofuran and ‐Dihydroindole Derivatives

Abstract

In this study, we have established a base‐mediated intramolecular vinylogous Mannich reaction, providing a straightforward approach for constructing structurally diverse dihydrobenzofuran and dihydroindole frameworks, which are commonly found in biologically active compounds. Presented herein is a sequential one‐pot base‐mediated reaction of salicylaldehyde imines/ ortho ‐tosylamidobenzaldimines and activated allyl bromides that undergoes O ‐/ N ‐allylation followed by an intramolecular vinylogous Mannich reaction, accessing 2‐alkenyl‐3‐aminophenyl‐dihydrobenzofuran and ‐dihydroindole derivatives with trans selectivity. The reaction proceeds efficiently across a wide range of substrates and affords the desired products in high yields with good diastereoselectivities. The reaction's scalability has been demonstrated through gram‐scale experiments, and post‐synthetic modifications have been presented.